Biomimetic vesicles and uses thereof

Abstract

The present disclosure relates to unimolecular core-shell nanoparticle, nanoclusters thereof, and platelet biomimetic nanoclusters thereof. The disclosed compositions are useful for treating a subject with a disease or condition, such as a cardiovascular disease. In a further aspect, the cardiovascular disease can be a vascular stenosis or restenosis. Also described herein are methods of making and using the unimolecular core-shell nanoparticle, nanoclusters thereof, and platelet biomimetic nanoclusters thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

1 . A unimolecular core-shell nanoparticle comprising:
 a functionalized polymer, wherein the functionalized polymer comprises a core-forming segment and a shell-forming segment.   
     
     
         2 . The unimolecular core-shell nanoparticle of  claim 1 , wherein the core-forming segment is a dendrimer or a hyperbranched polymer. 
     
     
         3 . The unimolecular core-shell nanoparticle of  claim 1 , wherein the core-forming segment is a dendrimer or hyperbranched polymer selected from the group consisting of: a bis-MPA dendrimer; a dendron, a PMAMAM dendrimer, a PEG-core dendrimer, a phosphorous dendrimer, and a polypropylenimine dendrimer. 
     
     
         4 . (canceled) 
     
     
         5 . The unimolecular core-shell nanoparticle of  claim 1 , wherein the core-forming segment is a PMAMAM dendrimer. 
     
     
         6 . The unimolecular core-shell nanoparticle of  claim 1 , wherein the shell-forming segment is a polymer selected from the group consisting of: a polyester, a polyamide, polyanhydride, and permissible co-polymers thereof. 
     
     
         7 . The unimolecular core-shell nanoparticle of  claim 1 , wherein the shell-forming segment is a polyester selected from the group of poly(valerolactone) (PVL), PLA, PLGA, PGA, PCL and co-polymers thereof. 
     
     
         8 . (canceled) 
     
     
         9 . The unimolecular core-shell nanoparticle of  claim 1 , wherein the functionalized polymer is functionalized with terminal negatively charged groups. 
     
     
         10 . (canceled) 
     
     
         11 . The unimolecular core-shell nanoparticle of  claim 1 , wherein the functionalized polymer is PAMP-PVL-COOH. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . The unimolecular core-shell nanoparticle of  claim 1 , further comprising a first pharmaceutical agent. 
     
     
         15 . (canceled) 
     
     
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         20 . The unimolecular core-shell nanoparticle of  claim 14 , wherein the first pharmaceutical agent is a protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibitor. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . The unimolecular core-shell nanoparticle of  claim 14 , the first pharmaceutical agent is a PI3K/p110α inhibitor, a CTPS1 inhibitor, a EZH2 inhibitor, a Smad3 inhibitor, a PDGFR inhibitor, a TGFBR inhibitor, a derivative thereof, a pharmaceutically acceptable salt thereof, or any combination thereof. 
     
     
         24 . (canceled) 
     
     
         25 . The unimolecular core-shell nanoparticle of  claim 14 , further comprising a second pharmaceutical agent; and wherein the second pharmaceutical agent is an anti-inflammatory agent, an anti-thrombogenic agent, a lipid lowering agent with endothelium protection function, an anti-hypertensive agent, other epigenetic inhibitors, or any combination thereof 
     
     
         26 . (canceled) 
     
     
         27 . A nanocluster comprising:
 a plurality of unimolecular core-shell nanoparticles as in  claim 1 .   
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . A biomimetic nanocluster comprising:
 a membrane structure comprising a first membrane component; and   a core structure comprising the nanocluster of claim  27 .   
     
     
         33 . (canceled) 
     
     
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         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . A method comprising:
 administering the or the biomimetic nanocluster of one of claim  32 .   
     
     
         44 . (canceled) 
     
     
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         48 . (canceled) 
     
     
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         50 . (canceled) 
     
     
         51 . A kit comprising:
 a unimolecular core-shell nanoparticle of  claim 1  to a subject; and   instructions to treat a subject with the unimolecular core-shell nanoparticle, the nanocluster, or the biomimetic nanocluster.   
     
     
         52 . (canceled) 
     
     
         53 . (canceled) 
     
     
         54 . (canceled)